1. Field of the Invention
This invention relates to an improved method for conducting peritoneal dialysis, and especially to an improved method of performing continuous internal peritoneal dialysis for the maintenance of patients with inadequate kidney function.
2. Description of the Art
Patients with chronic renal failure and anephric patients require a replacement, in one form or another, for the functions normally performed by the kidneys. These include the maintenance of fluid and electrolyte balance, the excretion of nitrogenous and other bodily wastes, the elimination of foreign molecules not removed by other means, and the retention of desirable body components present in the blood, such as nutrients and proteins. For those patients who cannot obtain or cannot sustain a transplant kidney, the only practical solution is an artificial kidney process of some sort (i.e. hemodialysis).
A widely used method of dialysis is extracorporeal hemodialysis. Here the patient's blood is cleansed by passing it through an artificial kidney in an artificial kidney dialysis machine.
A semipermeable membrane is interposed between the patient's blood and a suitably formulated dialysis solution. According to conventional theory, water, electrolytes, and other relatively small molecules diffuse in the direction of the osmotic gradient, which is determined by the formulation of the dialysis fluid. The dialysis fluid is so formulated that by the conclusion of the dialysis process, excess water, foreign compounds and nitrogenous wastes have diffused into the dialysate fluid. Proteins and other large molecules have been retained on the blood side of the membrane, and electrolyte concentrations have equilibrated on both sides of the dialysis membrane at normal levels.
The process of water removal by diffusion, from the patient's blood across the membrane is called ultrafiltration.
Extracorporeal hemodialysis is generally required three times per week, each session requiring 4 to 5 hours in a dialysis center or at home. During dialysis, the patient is "tied" to the machine by venous and arterial blood lines which convey the blood to and from the artificial kidney. The activities which the patient can perform are limited while the patient is "tied" to the machine. Thus, the patient's life is seriously affected as his or her daily activities must be planned around these sessions.
The dialysis process can be performed either outside the body as noted above by removing the blood and pumping it across any of the well known artificial semipermeable membranes, or in the body (endocorporeally), by placing a dialysis fluid in contact with a natural semipermeable membrane such as the peritoneal membrane (peritoneum). The peritoneum, which defines the peritoneal cavity, is a membrane lining the abdomen and pelvic walls. It contains many small blood vessels and capillary beds which act as a natural semipermeable membrane. In both extracorporeal and endocorporeal hemodialysis, impurities, toxins, and water in the blood are removed by diffusion across a membrane, a cellulose membrane of an artificial kidney or a peritoneal membrane of a peritoneal cavity respectively.
There are two types of such dialysis which utilize the peritoneal membrane, intermittent peritoneal dialysis and continuous ambulatory peritoneal dialysis.
With intermittent peritoneal dialysis a dialysate, typically containing glucose as an osmotic agent, is infused into the patient's peritoneal cavity by means of tubing and a catheter.
The dialysate remains in the patient's peritoneal cavity for a time sufficient for blood waste-products and water to be removed by diffusion across the peritoneal membrane and into the dialysate. The waste-products and water-containing dialysate then are drained from the peritoneal cavity by means of a catheter and tubing and a fresh supply of dialysate may be infused. Intermittent peritoneal dialysis (IPD) utilizes extracorporeal pumps or other auxilliary equipment to which the patient is "tied" during dialysis. The patient must remain sedentary while "tied" to the equipment. Here also, the patient's activities are seriously impeded.
For several reasons, an internal, continuous ambulatory (equilibrium) peritoneal dialysis process (CAPD) has features which cause it to be preferred by many patients. First, the patient can be ambulatory when an internal membrane is used because no pumping mechanism is needed and the key element required, the dialysis membrane, goes wherever the patient goes, i.e. the patient is not tied to a machine.
The patient need be sedentary only for the time required to drain and infuse dialysate from and into the peritoneal cavity.
In an intermittent external hemodialysis process, the high flow rates and rapid fluid or solute transfers involved tend to leave the patient exhausted after the dialysis, and higher levels of toxic wastes accumulate between dialyses. Both of these factors negatively affect the patient's sense of well being. The external hemodialysis process also requires repeated blood access which tends to cause vascular damage, wherein an internal peritoneal dialysis process does not require blood access.
Continuous dialysis using an equilibrium approach has been employed as a substitute for normal kidney function in thousands of patients. In a typical process, two liters of a suitably formulated dialysis solution, such as INPERSOL.RTM. Peritoneal Dialysis Solution, is infused into the peritoneal cavity through a permanently implanted peritoneal access catheter in the patient's abdominal wall.
Typically, when the dialysis solution container is empty, it is not disconnected from the tubing leading into the patient's peritoneal cavity. Instead, the patient simply rolls up or folds the container and tucks it into his clothing. The peritoneal access is thereby sealed and the solution is allowed to equilibrate for 4 to 6 hours. At the end of this period, the peritoneal access is opened and the spent dialysate is drained from the peritoneal cavity, again typically directly into the folded container and then discarded. The patient if necessary, replaces the container with fresh dialysate. The entire process can be repeated on a continuous basis, day and night, for as long as the patient requires a substitute kidney.
A disadvantage of the foregoing process is that the equilibration process occurs at different rates for different materials, depending upon molecular size, charge, and other factors Water, for example, equilibrates rapidly, flowing across the membrane and diluting the dialysis solution.
It has now been discovered that as water transfers across the membrane, it carries other small water-bound molecules with it. One such small molecule is urea, the principal nitrogenous metabolite produced by the body. Because of this phenomenon, urea transfer in the initial phase of the dialysis process has now been shown to be greater than can be accounted for by diffusion in response to an osmotic gradient.
However, once water equilibrates and the net transfer of water into the dialysis solution ceases, the urea is free to diffuse back across the membrane into the blood. Since this occurs fairly early in conventional continuous dialysis processes, it has now been shown that removal of small highly hydrated solutes is poorer in the continuous dialysis processes than in conventional intermittent processes in which an osmotic gradient is maintained and water transfer across the membrane occurs throughout the dialysis period.
Another disadvantage has already been mentioned. A substantial volume of excess water is removed from the body in the dialysis process, which is desirable. However, because the water transfers rapidly and equilibrates early in an equilibrium dialysis process, the patient is burdened with carrying the original volume of dialysis solution plus that large volume of fluid in the peritoneal cavity for the entire dialysis period.
Yet another disadvantage with the conventional internal continuous process is that it generally requires 4 to 6 fluid exchanges per day. Although these exchanges do not require blood access, each exchange presents an opportunity for microbial contamination. When contamination occurs, it frequently results in peritonitis, which requires intensive medical management and can ruin the peritoneum as a dialysis membrane. By reducing the number of exchanges required, an improved method would reduce the opportunity for such contamination and complications.
In view of these recognized disadvantages, there is an ongoing effort to improve the continuous internal dialysis process to make it safer and more effective for the patient. Such an improved process would also desirably be applicable to the acute dialysis of patients in need of such treatment, such as those suffering from poisonings and drug overdoses.
As used herein, the term "continuous" as in continuous ambulatory peritoneal dialysis (CAPD) means a substantially constant presence of a dialysate fluid which is maintained within a patient by a process of infusion, a definitive dwell time for the dialysis fluid within the peritoneal cavity and thereafter substantial removal of the modified dialysis composition. For maintenance of the patient, this procedure then requires repetition of the above noted steps. This is contrasted to use of the term "continual" in which the dialysis solution is added (or removed) in an ongoing manner, perhaps by utilization of a circulation loop, or by an infusion pump such as the Abbott/Parker Life Care 1500.RTM. ambulatory microinfuser, with resulting drainage of the fluid at a predetermined volume or osmolality concentration.
It has previously been suggested, in UK patent application No. 2,132,914, Milner et. al., that peritoneal dialysis solutions add glucose polymers to increase their osmotic pressure The adjustment of the osmolarity being within the needs of the clinician. Milner et. al. utilize a CAPD method with a single release of the osmotic agent(s) into the peritoneal cavity for each complete treatment, and since repeated treatments are used, the osmotic agent is released intermittently. A single infusion is administered with all of the active agent present and available at one time. The dialysis fluid is allowed to equilibrate with the body fluids, using a dwell time of about 4-6 hours.
PCT application WO 85/0555, Pearson et al. relates to the addition of monophosphoryl lipid A to a peritonial dialysis solution to suppress symptoms of peritonitis. Pearson et al. also utilizes the conventional CAPD methods for administration of the supplemented dialysis fluid.
Siefter et al., U.S. Pat. No. 3,911,915, issued Oct. 14, 1975 relates to a method of nourishment using maltose. An intraperitoneal (I.P.) injection of the iso-osmotic solution of maltose is administered five times daily. No fluid is removed from the peritoneal cavity. Siefter et al. thus teaches a method of parenteral nutrition. It does not teach, nor suggest the continual release of an osmotic agent into the cavity, nor maintenance of a substantially constant osmolarity of the dialysate solution.
Nolph et al. European patent application, 0,089,135 relates to the use of particulate sorbents in peritoneal dialysis solutions. Nolph et al., like the others defer to the prior art in so far as the formulations and methods of dialysis are concerned. Nolph et al. also observe that ultrafiltration occurs in their experimental system, and because of the design of that method the osmolarity of the dialysate must decrease with time as does the ultrafiltration rate. These decreases are precisely what the invention disclosed herein is meant to correct.